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Hisako Karube, Koju Kamoi, Kyoko Ohno-Matsui Department of Ophthalmology and Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan Background: Ocular symptoms in Behçet’s disease (BD) begin mostly before 30 years of age according to international surveys, and BD activity may decrease with age. Information regarding the treatment of ocular symptoms in elderly BD patients is thus scant. Anti-TNFα antibody has recently demonstrated strong effects against recurrent uveitis in BD, but the efficacy and safety of anti-TNFα therapy in elderly patients remain unclear. We report herein the case of an elderly patient with long-standing uveitis due to BD who was successfully treated with two types of anti-TNF therapy. Case: An 81-year-old Japanese man presented with a 33-year history of ocular inflammation due to BD. As immunosuppressive agents, such as cyclosporine A, were difficult to use because he had undergone removal of the left kidney due to cancer, he was treated with colchicine. However, attacks of ocular inflammation persisted around nine times a year. After colchicine had been changed to infliximab, ocular inflammation was fairly well controlled, but ocular attacks still occurred once or twice a year. As soon as intestinal hemorrhage related to BD occurred, infliximab was switched to adalimumab. After this switch, ocular attacks resolved and visual acuity was maintained at 1.0. Intestinal lesions were also well controlled, and no side effects were seen. Conclusion: This represents the first report of the application of two types of anti-TNFα therapy for ocular attacks in an elderly BD patient. In addition to infliximab, adalimumab appears to offer an alternative therapy for refractory, long-standing BD-related uveitis in elderly patients. Keywords: Behçet’s disease, anti-tumor necrosis factor-α antibody, infliximab, adalimumab, elderly patient

Abstract Background Tax is the oncoprotein of HTLV-1 which deregulates signal transduction pathways, transcription of genes and cell cycle regulation of host cells. Transacting function of Tax is mainly mediated by its protein-protein interactions with host cellular factors. As to Tax-mediated regulation of gene expression of HTLV-1 and cellular genes, Tax was shown to regulate histone acetylation through its physical interaction with histone acetylases and deacetylases. However, functional interaction of Tax with histone methyltransferases (HMTase) has not been studied. Here we examined the ability of Tax to interact with a histone methyltransferase SUV39H1 that methylates histone H3 lysine 9 (H3K9) and represses transcription of genes, and studied the functional effects of the interaction on HTLV-1 gene expression. Results Tax was shown to interact with SUV39H1 in vitro, and the interaction is largely dependent on the C-terminal half of SUV39H1 containing the SET domain. Tax does not affect the methyltransferase activity of SUV39H1 but tethers SUV39H1 to a Tax containing complex in the nuclei. In reporter gene assays, co-expression of SUV39H1 represses Tax transactivation of HTLV-1 LTR promoter activity, which was dependent on the methyltransferase activity of SUV39H1. Furthermore, SUV39H1 expression is induced along with Tax in JPX9 cells. Chromatin immunoprecipitation (ChIP) analysis shows localization of SUV39H1 on the LTR after Tax induction, but not in the absence of Tax induction, in JPX9 transformants retaining HTLV-1-Luc plasmid. Immunoblotting shows higher levels of SUV39H1 expression in HTLV-1 transformed and latently infected cell lines. Conclusion Our study revealed for the first time the interaction between Tax and SUV39H1 and apparent tethering of SUV39H1 by Tax to the HTLV-1 LTR. It is speculated that Tax-mediated tethering of SUV39H1 to the LTR and induction of the repressive histone modification on the chromatin through H3 K9 methylation may be the basis for the dose-dependent repression of Tax transactivation of LTR by SUV39H1. Tax-induced SUV39H1 expression, Tax-SUV39H1 interaction and tethering to the LTR may provide a support for an idea that the above sequence of events may form a negative feedback loop that self-limits HTLV-1 viral gene expression in infected cells.

Vaccination is a public health cornerstone that protects against numerous infectious diseases. Despite its benefits, immunization implications on ocular health warrant thorough investigation, particularly in the context of vaccine-induced ocular inflammation. This review aimed to elucidate the complex interplay between vaccination and the eye, focusing on the molecular and immunological pathways implicated in vaccine-associated ocular adverse effects. Through an in-depth analysis of recent advancements and the existing literature, we explored various mechanisms of vaccine-induced ocular inflammation, such as direct infection by live attenuated vaccines, immune complex formation, adjuvant-induced autoimmunity, molecular mimicry, hypersensitivity reactions, PEG-induced allergic reactions, Type 1 IFN activation, free extracellular RNA, and specific components. We further examined the specific ocular conditions associated with vaccination, such as uveitis, optic neuritis, and retinitis, and discussed the potential impact of novel vaccines, including those against SARS-CoV-2. This review sheds light on the intricate relationships between vaccination, the immune system, and ocular tissues, offering insights into informed discussions and future research directions aimed at optimizing vaccine safety and ophthalmological care. Our analysis underscores the importance of vigilance and further research to understand and mitigate the ocular side effects of vaccines, thereby ensuring the continued success of vaccination programs, while preserving ocular health.

Human T-cell leukemia virus type 1 (HTLV-1), a virus that affects 5-10 million people globally, causes several diseases, including adult T-cell leukemia-lymphoma and HTLV-1-associated uveitis (HU). HU is prevalent in Japan and often leads to secondary glaucoma, which is a serious complication. We investigated the efficacy of ripasudil, a Rho-associated coiled coil-forming protein kinase inhibitor, in alleviating changes in human trabecular meshwork cells (hTM cells) infected with HTLV-1. HTLV-1-infected hTM cells were modeled in vitro using MT-2 cells, followed by treatment with varying concentrations of ripasudil. We assessed changes in cell morphology, viability, and inflammatory cytokine levels, as well as NF-κB activation. The results showed that ripasudil treatment changed the cell morphology, reduced the distribution of F-actin and fibronectin, and decreased the levels of certain inflammatory cytokines, such as interleukin (IL)-6, IL-8, and IL-12. However, ripasudil did not significantly affect NF-κB activation or overall cell viability. These findings suggest that ripasudil has the potential to treat secondary glaucoma in patients with HU by modulating cytoskeletal organization and alleviating inflammation in HTLV-1-infected hTM cells. This study lays the foundation for further clinical studies exploring the effectiveness of ripasudil for the treatment of secondary glaucoma associated with HU.

Purpose: The purpose of this study was to determine the characteristics of staphyloma edges in highly myopic eyes and how they progress., Methods: We conducted a cross-sectional analysis using baseline data and a longitudinal study with follow-up data from 256 patients (447 eyes) with high myopia, with a mean (SD) follow-up of 3.79 (0.78) years. Participants were divided into four age groups: children (<13), youth (13-24), mature (25-59), and elderly (>60). Ultrawide-field swept-source optical coherence tomography was used to analyze staphyloma edges, which were divided into four areas: nasal to the optic disc (OD), superior to the macula, inferior to the macula, and temporal to the macula., Results: Staphylomas were significantly more prevalent in the mature (42.49%) and the elderly (51.35%) groups than in the children (13%) and youth (9%) groups. Staphyloma edges were predominantly superior to the macula in the mature and elderly groups. In contrast, staphylomas were rare in children and youth, with their edges mainly located nasal to the OD. The edges of staphylomas located superior and temporal to the macula were more likely to be associated with myopic traction maculopathy. During the follow-up period, 11 new staphyloma edges developed primarily in the mature group (64%). Additionally, 12 edges had an increased degree of protrusion over time, with most cases occurring in the mature (75%) group., Conclusions: The prevalence and location of staphyloma edges show significant variations depending on age. As time progresses, staphyloma edges manifest at distinct sites and increase their protrusion, potentially playing a role in the emergence of fundus complications.

We report a case of Vogt-Koyanagi-Harada (VKH) disease that recurred 46 years after initial treatment. A 59-year-old woman presented with a 2-month history of bilateral vision blurring. She had received her third dose of coronavirus disease 2019 (COVID-19) vaccination 4 months before the onset of blurring. The best-corrected visual acuity (BCVA) was 1.0 in the right eye and 0.15 in the left eye at the initial visit. Iritis and synechia were observed between the lens and iris bilaterally. A sunset glow fundus was found in both eyes with no serous retinal detachments or disc hyperemia. The patient had a history of VKH disease and had been treated with whole-body corticosteroid administration at another hospital when she was 13 years old. The patient was diagnosed with VKH disease recurrence, and oral corticosteroid therapy and corticosteroid eyedrop treatment were initiated. The treatment response was good. At the time of this writing, recurrence had not been observed for 14 months, and the BCVA was 1.0 in both eyes. To our knowledge, this case represents the longest recorded interval of VKH disease recurrence in the literature to date. COVID-19 vaccination might be the cause of long-term well-controlled disease recurrence., Competing Interests: Declaration of conflicting interestThe authors declare that there are no conflict of interests.

Since the introduction of combination antiretroviral therapy (cART) in Japan in 2008, the spectrum of ocular manifestations in patients with human immunodeficiency virus (HIV) has changed. This study, conducted at Tokyo Medical and Dental University Hospital between January 2012 and August 2023, aimed to understand the epidemiology and clinical features of ocular manifestations in patients with HIV during the cART era. Of the 218 patients diagnosed with HIV, 23 (10.55%) exhibited ocular manifestations; all were male, aged 32-73. The most prevalent ocular complication was uveitis (60.67%). Notably, the prevalence of uveitis in this cART era has surged compared to earlier Japanese studies. Our data also suggest a potential direct link between uveitis and HIV, particularly in patients who have not yet undergone cART. However, cytomegalovirus retinitis, another prevalent ocular disease in our study, appeared more strongly associated with patients who commenced cART. Neither ocular condition was significantly correlated with CD4+ T-cell count. Importantly, our observed ocular manifestation prevalence (10.55%) was lower than that in previous studies, emphasizing the potential influence of cART and national healthcare support. These findings provide unique insights into the evolution of ocular manifestations in patients with HIV in Japan amidst cART availability.

We herein describe a patient who developed recurrence of macular edema (ME) due to branch retinal vein occlusion (BRVO) 3 days after administration of the BNT162b2 vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A man in his early 50s visited our hospital because of vision loss in his right eye. His logarithmic best-corrected visual acuity (BCVA) was -0.79 in both eyes. ME due to superior temporal BRVO was observed in his right eye, and the central foveal thickness (CFT) was 486 µm. The patient was treated with an intravitreal aflibercept injection with logarithmic BCVA of -0.79, leading to resolution of the ME with a CFT of 299 µm. Three months after the initial visit, he received a fourth dose of an mRNA vaccine. Three days later, he developed vision loss in his right eye. Although the logarithmic BCVA was maintained at -0.79, ME recurred with a CFT of 507 µm. The patient was treated with an additional dose of intravitreal aflibercept injection. The ME resolved and the logarithmic BCVA in the right eye was maintained at -0.79. This case indicates a possible association between vaccination against SARS-CoV-2 and recurrence of ME due to BRVO., Competing Interests: Declaration of conflicting interestsThe authors declare that there is no conflict of interest.

The association between vaccines and ocular disorders has attracted significant attention in scientific research. Numerous mainstream vaccines are associated with a range of uveitis types, including anterior, intermediate, and posterior uveitis. Additionally, they are associated with distinct ocular diseases such as multifocal choroiditis, Vogt-Koyanagi-Harada (VKH) disease, acute posterior multifocal placoid pigment epitheliopathy (APMPPE), and multiple evanescent white dot syndrome (MEWDS). These ocular conditions are often transient, with a vast majority of patients experiencing improvement after steroid intervention. To date, numerous cases of vaccine-induced uveitis have been reported. This study analyzed the correlation between antiviral vaccines, including the hepatitis B virus (HBV), human papillomavirus (HPV), measles-mumps-rubella (MMR), varicella zoster virus (VZV), and influenza vaccines, and different manifestations of uveitis. This is the first comprehensive study to offer a detailed analysis of uveitis types induced by antiviral vaccines. Through an extensive database search, we found a particularly strong link between influenza vaccines, followed by VZV and HPV vaccines. While anterior uveitis is common, conditions such as APMPPE, MEWDS, and VKH are particularly notable and merit careful consideration in clinical practice. Corticosteroid treatment was effective; however, half of the observed patients did not achieve full recovery, indicating potentially prolonged effects of the vaccine.

Restoration of immunological tolerance to self antigens has been a major drive in understanding the mechanisms of, and developing new treatments for, autoimmune and autoinflammatory disease. Sessile dendritic cells (DC) are considered the main instruments underpinning immunological tolerance particularly the CD205 + (DEC205 + ) cDC1 subset in contrast to DCIR2 + cDC2 which mediate immunogenicity. Targeting DC using autoantigen peptide-antibody fusion proteins has been a well explored methodology for inducing tolerance. Here we show that subcutaneous (s.c.) inoculation of hen-egg lysozyme (HEL)-DEC205 Ig fusion prevents the development of spontaneous uveoretinitis (experimental autoimmune uveoretinitis, EAU) in a transgenic mouse model generated by crossing interphotoreceptor retinol binding protein (IRBP)-HEL (sTg HEL) with HEL specific TCR (sTg TCR) mice. Prolonged suppression of EAU required injections of HEL-DEC205 Ig once weekly, reflecting the half life of s.c. DC. Interestingly, HEL-DCIR2 Ig also had a suppressive effect on development of EAU but less so than DEC205 Ig while it had minimal effect on preventing the retinal atrophy associated with EAU. In addition, HEL-DEC205 Ig was only effective when administered s.c. rather than systemically and had no effect on EAU induced by adoptive transfer of HEL-activated T cells. These data demonstrate the importance of systemic (lymph node) rather than local (eye) antigen presentation in the development of EAU as well as suggest a potential therapeutic approach to controlling sight-threatening immune-mediated uveitis provided relevant antigen(s) can be identified., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Klaska, Yu, Fordyce, Kamoi, Cornall, Martin-Granados, Kuffova and Forrester.)

Purpose: This case report presents a direct composite inverse injection technique using a bi-layer clear mini-index fabricated with a digital workflow to restore extensive posterior occlusal cavities in a 13-year-old patient., Materials and Methods: After a root canal treatment in the right mandibular first molar and step-wise excavation of deep caries in the left mandibular first molar, the extensive occlusal restorations were digitally designed using CAD software, upon which digital wax-ups were 3D-printed. Bi-layer clear mini-indices consisting of a hard outer plastic layer and an elastic inner silicone layer were prepared from the 3D-printed cast. The bonding surfaces were deproteinized using a 6% sodium hypochlorite solution, and an antioxidant (Clearfil DC Activator; Kuraray Noritake) was utilized to improve the dentin bonding durability of a 2-step self-etch adhesive (Clearfil SE Bond 2; Kuraray Noritake). Subsequently, a highly filled universal-shade flowable resin composite (RC) was incrementally placed into the cavities. To create the final occlusal morphology, the same RC was inversely injected through the opening of the bi-layer indices., Results: The workflow was feasible, and the occlusal cavities were efficiently restored using the injection technique. Occlusal carving and adjustments of the morphology were not necessary, leading to less chair time. At the 1-year follow-up, the clinical outcome was excellent., Conclusion: The injection technique with a bi-layer clear mini-index accurately translated the digital wax-ups into large, final restorations. Precise morphology and shortened chair time enhanced patient satisfaction, but at the expense of multiple visits.

Viruses account for 80% of all cases of acute conjunctivitis and adenovirus; enterovirus and herpes virus are the common causative agents. In general, viral conjunctivitis spreads easily. Therefore, to control the spread, it is crucial to quickly diagnose illnesses, strictly implement hand washing laws, and sanitize surfaces. Swelling of the lid margin and ciliary injection are subjective symptoms, and eye discharge is frequently serofibrinous. Preauricular lymph node swelling can occasionally occur. Approximately 80% of cases of viral conjunctivitis are caused by adenoviruses. Adenoviral conjunctivitis may become a big global concern and may cause a pandemic. Diagnosis of herpes simplex viral conjunctivitis is crucial for using corticosteroid eye solution as a treatment for adenovirus conjunctivitis. Although specific treatments are not always accessible, early diagnosis of viral conjunctivitis may help to alleviate short-term symptoms and avoid long-term consequences.

At present, the world is at the tipping point of the outbreak of mpox. The World Health Organization has declared the current mpox outbreak a 'public health emergency of international concern'. Mpox has been shown to be associated with several ocular manifestations. Given the current state of the mpox outbreak, healthcare providers, particularly ophthalmologists, need to be aware of these ophthalmic symptoms and how to manage them. In this review, we highlight current knowledge on the ocular symptoms of mpox virus (MPXV) infections and how to detect them. In addition, we summarize the treatment strategies for these ocular manifestations of MPXV infections and outline the relationship between vaccination and the ocular symptoms of mpox.

Uveitis is one of the most common ocular complications in people living with the Human immunodeficiency virus (HIV) and can be classified into HIV-induced uveitis, co-infection related uveitis, immune recovery uveitis, and drug-induced uveitis. The introduction of antiretroviral therapy has considerably changed the incidence, diagnosis, and treatment of different types of HIV-related uveitis. Furthermore, the specific immune condition of patients infected with HIV makes diagnosing HIV-related uveitis difficult. Recent studies have focused on the growing prevalence of syphilis/tuberculosis co-infection in uveitis. Simultaneously, more studies have demonstrated that HIV can directly contribute to the incidence of uveitis. However, the detailed mechanism has not been studied. Immune recovery uveitis is diagnosed by exclusion, and recent studies have addressed the role of biomarkers in its diagnosis. This review highlights recent updates on HIV-related uveitis. Furthermore, it aims to draw the attention of infectious disease physicians and ophthalmologists to the ocular health of patients infected with HIV.

Introduction: HTLV-1 (human T-cell lymphotropic virus type 1) is a retrovirus that infects approximately 20 million people worldwide. Many diseases are caused by this virus, including HTLV-1-associated myelopathy, adult T-cell leukemia, and HTLV-1 uveitis. Intraocular anti-vascular endothelial growth factor (VEGF) antibody injection has been widely used in ophthalmology, and it is reportedly effective against age-related macular degeneration, complications of diabetic retinopathy, and retinal vein occlusions. HTLV-1 mimics VEGF 165 , the predominant isoform of VEGF, to recruit neuropilin-1 and heparan sulfate proteoglycans. VEGF 165 is also a selective competitor of HTLV-1 entry. Here, we investigated the effects of an anti-VEGF antibody on ocular status under conditions of HTLV-1 infection in vitro ., Methods: We used MT2 and TL-Om1 cells as HTLV-1-infected cells and Jurkat cells as controls. Primary human retinal pigment epithelial cells (HRPEpiCs) and ARPE19 HRPEpiCs were used as ocular cells; MT2/TL-Om1/Jurkat cells and HRPEpiCs/ARPE19 cells were co-cultured to simulate the intraocular environment of HTLV-1-infected patients. Aflibercept was administered as an anti-VEGF antibody. To avoid possible T-cell adhesion, we lethally irradiated MT2/TL-Om1/Jurkat cells prior to the experiments., Results: Anti-VEGF antibody treatment had no effect on activated NF-κB production, inflammatory cytokines, chemokines, HTLV-1 proviral load (PVL), or cell counts in the retinal pigment epithelium (RPE) under MT2 co-culture conditions. Under TL-Om1 co-culture conditions, anti-VEGF antibody treatment did not affect the production of activated NF-κB, chemokines, PVL, or cell counts, but production of the inflammatory cytokine IL-6 was increased. In addition, anti-VEGF treatment did not affect PVL in HTLV-1-infected T cells., Conclusion: This preliminary in vitro assessment indicates that intraocular anti-VEGF antibody treatment for HTLV-1 infection does not exacerbate HTLV-1-related inflammation and thus may be safe for use., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer MM declared a shared affiliation with the authors to the handling editor at the time of review., (Copyright © 2023 Zong, Kamoi, Kurozumi-Karube, Zhang, Yang and Ohno-Matsui.)

Purpose: To evaluate 10-year outcome of infliximab (IFX) treatment for uveitis in Behçet disease (BD) patients using a standardized follow-up protocol., Design: Retrospective longitudinal cohort study., Participants: 140 BD uveitis patients treated with IFX enrolled in our previous study., Methods: Medical records were reviewed for demographic information, duration of IFX treatment, number of ocular attacks before IFX initiation, best corrected visual acuity (VA) at baseline and 1, 2, 3, 4, 5, and 10 years after IFX initiation, uveitis recurrence after IFX initiation and main anatomical site, concomitant therapies, and adverse events (AEs)., Main Outcome Measures: 10-year IFX continuation rate and change in LogMAR VA., Results: Of 140 BD patients, 106 (75.7%) continued IFX treatment for 10 years. LogMAR VA improved gradually after initiation of IFX, and the improvement reached statistical significance from 2 years of treatment. Thereafter, significant improvement compared with baseline was maintained until 10 years, despite a slight deterioration of logMAR VA from 5 years. However, eyes with worse baseline decimal VA < 0.1 showed no significant improvement from baseline to 10 years. Uveitis recurred after IFX initiation in 50 patients (recurrence group) and did not recur in 56 (non-recurrence group). Ocular attacks/year before IFX initiation was significantly higher in the recurrence group (2.82 ± 3.81) than in the non-recurrence group (1.84 ± 1.78). In the recurrence group, uveitis recurred within 1 year in 58% and within 2 years in 74%. Seventeen patients (34%) had recurrent anterior uveitis, 17 (34%) had posterior uveitis, and 16 (32%) had panuveitis, with no significant difference in VA outcome. In addition, logMAR VA at 10 years did not differ between the recurrence and non-recurrence groups. AEs occurred among 43 patients (30.7%), and 24 (17.1%) resulted in IFX discontinuation before 10 years., Conclusions: Among BD patients with uveitis who initiated IFX, approximately 75% continued treatment for 10 years, and their VA improved significantly and was maintained for 10 years. Uveitis recurred in one-half of the patients, but visual acuity did not differ significantly from the patients without recurrence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Takeuchi, Usui, Namba, Keino, Takeuchi, Takase, Kamoi, Hase, Ito, Nakai, Maruyama, Kobayashi, Mashimo, Sato, Ohguro, Hori, Okada, Sonoda, Mizuki and Goto.)

Little is known regarding anterior uveitis (AU), the most common ocular disease associated with cytomegalovirus (CMV) infection in immunocompetent populations. CMV AU is highly prevalent in Asia, with a higher incidence in men. Clinically, it manifests mainly as anterior chamber inflammation and elevated intraocular pressure (IOP). Acute CMV AU may resemble Posner-Schlossman syndrome with its recurrent hypertensive iritis, while chronic CMV AU may resemble Fuchs uveitis because of its elevated IOP. Without prompt treatment, it may progress to glaucoma; therefore, early diagnosis is critical to prognosis. Knowledge regarding clinical features and aqueous humor analyses can facilitate accurate diagnoses; so, we compared and summarized these aspects. Early antiviral treatment reduces the risk of a glaucoma surgery requirement, and therapeutic effects vary based on drug delivery. Both oral valganciclovir and topical ganciclovir can produce positive clinical outcomes, and higher concentration and frequency are beneficial in chronic CMV retinitis. An extended antiviral course could prevent relapses, but should be limited to 6 months to prevent drug resistance and side effects. In this review, we have systematically summarized the pathogenesis, clinical features, diagnostic and therapeutic aspects, and immunological mechanisms of CMV AU with the goal of providing a theoretical foundation for early clinical diagnosis and treatment.

Introduction: Myopic macular neovascularization (MNV) is the most common cause of a reduction of central vision in eyes with pathologic myopia, and it can progress to macular atrophy in the long term. The aim of this study was to determine the risk factors associated with the development of MNVs., Methods: There were 17,198 follow-up records from 5,409 eyes of 2,784 highly myopic patients that were reviewed. The general information and ophthalmic information in the records were studied. The significance of the correlations of factors associated with the development and predicting the development of myopic MNV were determined., Results: Being a woman (odds ratio [OR] = 0.727, p < 0.001), having a longer axial length (OR = 0.948, p < 0.001), having a poorer baseline best-correct visual acuity (BCVA, OR = 2.098, p < 0.001), having severe myopic maculopathy (overall: p < 0.001), prior myopic MNV in the fellow eye (OR = 4.105, p < 0.001), presence of patchy atrophy (overall p < 0.001), lacquer cracks (OR = 1.718, p < 0.001), prior foveal retinal detachment (RD, OR = 3.269, p < 0.001), prior macular hole (MH, OR = 0.641, p < 0.001), prior macular retinoschisis (OR = 1.533, p < 0.001), and prior macular edema (OR = 1.508, p < 0.001) were significantly correlated with the development of myopic MNV. Eyes with MNV and patchy atrophy would require an intensive follow-up examination for myopic patients as the fellow eye would have a risk of >70% for the development of myopic MNV in 3 years and nearly 80% in 5 years., Conclusions: Clinicians need to pay special attention to eyes with severe grades of myopic maculopathy, prior myopic MNV in the fellow eye, presence of patchy atrophy, and prior foveal retinal detachment to determine the onset of myopic MNV., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Purpose: To determine the prevalence, characteristics, and causes of papillary and peripapillary hemorrhages (PPHs) in eyes with pathologic myopia (PM)., Methods: PM patients were retrospectively studied between 2011 and 2018. Fundus images were used to diagnose and classify the PPHs. Fundus fluorescein angiographic (FFA) and optical coherence tomographic (OCT) images were used to determine the status of the retinal vessels and tissue at and around the PPH sites. Visual field data determined by Goldmann perimetry and Humphrey visual field analyzer were also analyzed., Results: A total of 2171 PM patients (3774 eyes) were examined. Eighty-eight patients (97 eyes) had PPHs (mean age 66.8 ± 11.9 years; mean axial length 30.79 ± 2.17 mm) for a prevalence of 4.05%. Thirty (30.9%) eyes recurred. Among the 90 eyes with a single-site PPH, the most common type and location were the conus type (49 eyes, 54.4%) and the temporal side (66 eyes, 73.3%), respectively. Regression analysis showed that patchy atrophy reduced the risk of recurrences than diffuse atrophy (P < 0.05), whereas a longer axial length and potential glaucoma increased the risk (both P < 0.05). FFA and OCT showed that PPHs developed in the area of straightened retinal arterioles (24 eyes), at or beside the peak of a ridge (10 eyes), in an area of compressed retinal tissue (two eyes)., Conclusions: PPHs are present in 4.05% of PM eyes, and they are most often located in the temporal peripapillary atrophic region of the retina. Axial elongation, mild myopic maculopathy, and potential glaucoma are risk factors for recurrences.

Aim: To investigate the causes of low prevalence of Fuchs' uveitis syndrome (FUS) in Japan., Methods: Medical records of 160 patients diagnosed with FUS at 14 uveitis specialty facilities in Japan were reviewed retrospectively., Results: In 160 FUS patients, mean follow-up period before referral to our uveitis facilities was 31.6 ± 50.9 months. The most common reason for referral was idiopathic uveitis (61.9%), followed by cataract (25.0%), high intraocular pressure (IOP) including glaucoma (16.3%), and FUS (14.4%). Unilateral involvement was 96.9%. The most frequent ocular finding of FUS was anterior inflammation (91.9%), followed by stellate-shaped keratic precipitates (88.1%), cataract/pseudophakia (88.1%), diffuse iris atrophy (84.4%), vitreous opacity (62.5%), heterochromia (53.1%) and high IOP including glaucoma (36.3%). As treatments of these ocular findings, cataract surgery was performed in 52.5%, glaucoma surgery in 10.6%, and vitrectomy in 13.8%. Mean logMAR VA was 0.28 ± 0.59 at the initial visit, and decreased significantly to 0.04 ± 0.32 at the last visit. Proportions of FUS patients with BCVA <0.1 and 0.1 to <0.5 decreased, while that of ≥0.5 increased at the last visit compared with the initial visit., Conclusions: Ocular findings of FUS in Japanese FUS patients were consistent with the characteristic features. The low prevalence of FUS in Japan may be a result of being overlooked and misdiagnosed as mild idiopathic uveitis, cataract, and/or glaucoma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yoneda, Usui, Tanaka, Hase, Namba, Kamoi, Takase, Takeuchi, Matsumiya, Kusuhara, Takeda, Yawata, Yanai, Hiyama, Harada, Hashida, Maruyama, Nakai, Taguchi, Kaburaki, Mizuki, Goto, Fujino and Takeuchi.)

Human T-cell lymphotropic virus type 1 (HTLV-1) was the first retrovirus identified as the causative agent of human diseases, such as adult T-cell leukemia, HTLV-1-associated myelopathy, and HTLV-1 uveitis (HU). HU is one of the most frequent ocular inflammatory diseases in endemic areas, which has raised considerable public health concerns. Approximately 30% of HU patients develop secondary glaucoma, which is higher than the general uveitis incidence. We therefore investigated the mechanism underlying the high incidence of glaucoma secondary to HU in vitro. After contact with HTLV-1-producing T cells (MT-2), human trabecular meshwork cells (HTMCs) were infected. The infected cells increased in number, and nuclear factor (NF)-κB expression was activated. Contact between MT-2 cells and HTMCs resulted in significantly upregulated production of inflammatory cytokines, such as IL-6, and chemokines, such as CXCL10, CCL2, and CXCL-8. These findings indicate that the mechanism underlying secondary glaucoma in HU may involve proliferation of trabecular meshwork tissue after contact with HTLV-1-infected cells, resulting in decreased aqueous humor outflow. Upregulated production of inflammatory cytokines and chemokines simultaneously disrupts the normal trabecular meshwork function. This mechanism presumably leads to increased intraocular pressure, eventually resulting in secondary glaucoma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zong, Kamoi, Ando, Kurozumi-Karube and Ohno-Matsui.)

HTLV-1 uveitis (HU) is the third clinical entity to be designated as an HTLV-1-associated disease. Although HU is considered to be the second-most frequent HTLV-1-associated disease in Japan, information on HU is limited compared to that on adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy (HAM). Recent studies have addressed several long-standing uncertainties about HU. HTLV-1-related diseases are known to be caused mainly through vertical transmission (mother-to-child transmission), but emerging HTLV-1 infection by horizontal transmission (such as sexual transmission) has become a major problem in metropolitan areas, such as Tokyo, Japan. Investigation in Tokyo showed that horizontal transmission of HTLV-1 was responsible for HU with severe and persistent ocular inflammation. The development of ATL and HAM is known to be related to a high provirus load and hence involves a long latency period. On the other hand, factors contributing to the development of HU are poorly understood. Recent investigations revealed that severe HU occurs against a background of Graves' disease despite a low provirus load and short latency period. This review highlights the recent knowledge on HU and provides an update on the topic of HU in consideration of a recent nationwide survey.

Purpose: To identify structural abnormalities in the papillary and peripapillary area in eyes with pathologic myopia (PM) and normal IOP and to determine their relationship to visual field (VF) defects., Methods: One hundred eight eyes of 70 patients with PM were retrospectively studied. The disc-centered swept source optical coherence tomographic images and the Goldmann VF recorded within 1 year of the optical coherence tomographic examination were analyzed. Four structural abnormalities were identified: lamina cribrosa (LC) defects, ridge protrusions, intrachoroidal cavitations (ICC), and prelaminar schisis. The correspondence of the VF defects with the structural abnormalities was assessed., Results: The mean age, axial length, and optic disc area of the 108 eyes were 58.7 ± 10.0 years, 31.1 ± 2.4 mm, and 4.7 ± 2.2 mm2, respectively. Eighty-five of the 108 eyes (78.7%) had at least one abnormality and 49.4% (42/85) had two or more abnormalities. LC defects, ridge protrusions, ICC, and prelaminar schisis were detected in 47.2%, 33.3%, 21.3%, and 30.6% of the eyes, respectively. VF defects at the corresponding areas of these structural abnormalities were seen in 63% of the eyes with LC defects, 39% of the eyes with ridge protrusions, and 21% of the eyes with ICC., Conclusions: Four kinds of structural abnormalities with corresponding VF defects are commonly observed in the papillary and peripapillary region of eyes with PM. The presence of these abnormalities suggests a possibility of functional damage.

Little is known about the long-term incidence of posterior capsule opacification (PCO) after cataract surgery in patients with uveitis. This retrospective study included 211 eyes of 146 patients with non-infectious uveitis who underwent cataract surgery and implantation of an Acrysof SN60WF (Surface: plasma-treated, Optic and Haptic: hydrophobic acrylic), iSert XY-1 (Surface: UV-ozone-treated, Optic and Haptic: hydrophobic acrylic), or iSert 251/255 (Surface: UV-ozone-treated, Optics: hydrophobic acrylic, Haptic: polymethyl methacrylate). The cumulative incidences of PCO and subsequent yttrium-aluminum-garnet (Nd:YAG) capsulotomy over the 5-year follow-up were analyzed, and patients who were implanted with different intraocular lenses (IOLs) were compared. Mixed-effects Cox proportional hazard models showed that, compared with the Acrysof group, the iSert XY-1 group had higher risks of PCO (adjusted HR, 7.26; 95% CI, 1.82-28.8) and Nd:YAG capsulotomy (adjusted HR, 6.50; 95% CI, 1.55-27.2). Similar results were obtained when the Acrysof group was compared with the iSert 251/255 group for PCO (adjusted HR, 8.22; 95% CI, 2.35-28.7) and Nd:YAG capsulotomy (adjusted HR, 8.26; 1.90-36.0). These data suggest that a plasma-treated surface, hydrophobic acrylic optic and hydrophobic acrylic haptic, of the IOL could enhance biocompatibility even under inflammatory conditions, thus suppressing PCO development., (© 2022. The Author(s).)

Nonplatinum metal (NPM) catalysts for the oxygen reduction reaction (ORR) in proton exchange membrane fuel cells (PEMFCs) have been developed; however, NPM catalysts still need to be improved in terms of both their catalytic activity and durability. To overcome these problems, an Fe active site contained within a more compact ligand than conventional, porphyrinic, 16-membered ring ligands, or more specifically, a hexaaza macrocyclic ligand with a 14-membered ring (14MR), was developed. In this study, the durability of the Fe-14MR complex was compared to that of Fe phthalocyanine (FePc), which has a 16-membered ring ligand, using in situ X-ray absorption spectroscopy; demetalation of the Fe complexes was directly observed during electrochemical experiments performed under acidic ORR conditions. It was found that Fe-14MR is significantly more resistant to demetalation than FePc during the ORR., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Purpose: To determine whether the hyporeflective areas in the blue images obtained by widefield scanning laser ophthalmoscopy (SLO) correspond to the non-perfused areas (NPAs) in the fluorescein angiograms (FA) in eyes with diabetic retinopathy (DR)., Design: Retrospective observational case series., Methods: Ninety patients with diabetes mellitus (DM) were studied. All had undergone multicolor widefield SLO imaging. The NPAs in the FA images and hyporeflective areas in the blue widefield SLO images were examined. The morphology of the retina was determined by optical coherence tomography., Results: Hyporeflective areas in the blue SLO images were found with a rate of 76.6% in eyes with proliferative DR eyes. In a comparison of the hyporeflective areas of the blue SLO images to the non-perfused areas in the FA images, the appearance and the correspondence in the locations of these two types of images were found, and the rate was highly concordant with a Cohen's kappa value of 0.675., Conclusions: The high concordance between the hyporeflective areas in the widefield blue SLO and the NPAs in the FA indicates that widefield blue SLO can be used to identify ischemic retinal areas in eyes with DR without the intravenous injection of any dye., (Copyright © 2021 Asia-Pacific Academy of Ophthalmology. Published by Wolters Kluwer Health, Inc. on behalf of the Asia-Pacific Academy of Ophthalmology.)

Adalimumab (ADA), a fully human monoclonal tumor necrosis factor (TNF)-α antibody, is one of the most widely used biologics in the treatment of inflammatory diseases. However, ADA can exacerbate infectious conditions, induce paradoxical reactions such as inflammation, and cause neoplasia. Human T-cell leukemia virus type 1 (HTLV-1) is an infectious agent that induces inflammation and neoplastic infiltration in the eye. To date, numerous HTLV-1 carriers have been treated with adalimumab to suppress inflammation out of necessity, when standard anti-inflammatory drugs such as steroids and immunosuppressive agents have proven inadequate to control the inflammation. Here, we clarify the safety of adalimumab for the eye under HTLV-1 infectious conditions in vitro . We used the adult retinal pigment epithelial cell line (ARPE)-19 cell line as ocular resident cells, and used MT2 and TL-Om1 as HTLV-1-infected cells. ARPE-19 and MT2/TL-Om1 were co-cultured, and then adalimumab was administered. Production of cytokines and chemokines, TNF-α receptor (TNF-R), HTLV-1 proviral load (PVL), and apoptosis were measured to assess the effects of adalimumab. Contact between ARPE-19 and MT2/TL-Om1 produced inflammatory cytokines such as TNF, interleukin (IL)-6, IL-8 and IL-10, and transduced chemokines such as interferon-inducible protein-10 (IP-10), monocyte chemotactic protein-1 (MCP-1), monokine induced by interferon-γ (MIG), and regulated on activation, normal T cell expressed and secreted (RANTES). No inflammatory cytokines and chemokines were exacerbated by adalimumab. Expression of TNF-R on ARPE-19 and MT2/TL-Om1 cells, HTLV-1 PVLs of MT2/TL-Om1 cells, and cell growth rate and apoptotic rate of ARPE-19 were unaffected by adalimumab. In conclusion, adalimumab does not appear to exacerbate HTLV-1-associated inflammatory conditions in the eye or increase PVL in HTLV-1-infected T cells. These data suggest that adalimumab could be used safely for the eye under HTLV-1 infectious conditions from the perspective of in vitro assessment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Kurozumi-Karube, Kamoi, Ando, Uchida, Hamaguchi and Ohno-Matsui.)

Infliximab (IFX) was the first biologic introduced for refractory uveitis treatment in Behçet's syndrome (BS). However, there have been few reports on the safety and efficacy of IFX monotherapy over follow-up periods of more than 10 years. This retrospective study evaluated the 10-year safety and efficacy of IFX monotherapy compared to IFX combination therapies with colchicine or corticosteroid for refractory uveitis in BS patients. Monotherapy was performed in 30 eyes of 16 patients while combination therapies were performed in 20 eyes of 11 patients. Continuation of IFX occurred in 70.3% of enrolled patients for 10 years without any significant difference noted in the retention rate between the monotherapy and combination therapies (p = 0.86). Reduction of ocular inflammatory attacks and improvement of best corrected visual acuity occurred in the monotherapy group after 10 years, which was equivalent to that for the combination therapies. Although adverse events (AEs) or therapy discontinuation occurred during the initial 5 years in both therapies, no AEs were observed for either therapy after 6 years. Our results suggested that IFX monotherapy proved to be effective and not inferior to combination therapies over a 10-year follow-up. Although loss of response and AEs may be noticed during the initial 5-year period, a safe and effective continuation can be expected thereafter.

We specify the clinical features of a spontaneous experimental autoimmune uveitis (EAU) model, in which foreign hen-egg lysozyme (HEL) is expressed in the retina, controlled by the promoter for interphotoreceptor retinol binding protein (IRBP). We previously reported 100% P21 (post-partum day) IRBP:HEL single transgenic (sTg) mice, when crossed to transgenic T cell receptor mice (3A9) generating the double transgenic (dTg) genotype, develop EAU despite profound lymphopenia (thymic HEL-specific T cell deletion). In this work, we characterized the immune component of this model and found conventional dTg CD4+ T cells were less anergic than those from 3A9 controls. Furthermore, prior in vitro HEL-activation of 3A9 anergic T cells (T an ) rendered them uveitogenic upon adoptive transfer (Tx) to sTg mice, while antigen-experienced (AgX, dTg), but not naïve (3A9) T cells halted disease in P21 dTg mice. Flow cytometric analysis of the AgX cells elucidated the underlying pathology: FoxP3+CD25 hi CD4+ T regulatory cells (T reg ) comprised ∼18%, while FR4+CD73+FoxP3-CD25 lo/- CD4+ T an comprised ∼1.2% of total cells. Further T reg -enrichment (∼80%) of the AgX population indicated FoxP3+CD25 hi CD4+ T reg played a key role in EAU-suppression while FoxP3-CD25 lo/- CD4+ T cells did not. Here we present the novel concept of dual immunological tolerance where spontaneous EAU is due to escape from anergy with consequent failure of T reg induction and subsequent imbalance in the [T reg :T effector ] cell ratio. The reduced numbers of T an , normally sustaining T reg to prevent autoimmunity, are the trigger for disease, while immune homeostasis can be restored by supplementation with AgX, but not naïve, antigen-specific T reg ., (Copyright © 2020 Liu, Mölzer, Makinen, Kamoi, Corbett, Klaska, Reid, Wilson, Kuffová, Cornall and Forrester.)

Human T-cell leukemia virus type 1 (HTLV-1) was the first retrovirus described as a causative agent for human disease. In the field of ophthalmology, a close relationship between HTLV-1 infection and uveitis was identified through a series of clinical and laboratory studies in the late 1980s-1990s. Since then, HTLV-1-related ocular manifestations such as keratoconjunctivitis sicca, interstitial keratitis, optic neuritis and adult T-cell leukemia/lymphoma (ATL)-related ocular manifestations have continuously been reported. During the three decades since the association between HTLV-1 and ocular pathologies was discovered, ophthalmic practice and research have advanced with the incorporation of new technologies into the field of ophthalmology. Accordingly, new findings from recent research have provided many insights into HTLV-1-associated ocular diseases. Advanced molecular technologies such as multiplex polymerase chain reaction (PCR)/broad-range PCR using ocular samples have enabled rapid and accurate diagnosis. Advanced ophthalmic technologies such as widefield fundus camera and optical coherence tomography (OCT) have clarified various features of HTLV-1-associated ocular manifestations, and identified characteristics such as the "knob-like ATL cell multiple ocular infiltration" (KAMOI) sign. Advanced drug delivery methods such as intravitreal injection and sub-Tenon injection have led to progress in preventing disease progression. This article describes global topics and the latest research findings for HTLV-1-associated ocular diseases, with reference to a large-scale nationwide survey of ophthalmologists. Current approaches and unmet needs for HTLV-1 infection in ophthalmology are also discussed., (Copyright © 2020 Kamoi.)

Rationale: Proliferation of retinal pigment epithelium (RPE) is typically observed in limited ocular disorders, in connection with the local mechanism of RPE proliferation-mediated wound repair. Bilateral and diffuse type RPE proliferation is considered to be associated with paraneoplastic syndromes, such as a bilateral diffuse uveal melanocytic proliferation. However, other reported diseases that induce bilateral diffuse RPE proliferation are quite rare, especially for patients who are considered to have a non-malignant status., Patient Concerns: The bilateral eyes of a 47-year-old woman with bilateral ocular inflammation, presented united multiple small to medium white retinal lesions during the disease progress., Diagnoses: Optical coherence tomography showed scattered serous retinal detachments, choroidal folds, choroidal thickening and diffuse RPE proliferation. As autofluorescence and angiography showed a "giraffe pattern", bilateral diffuse uveal melanocytic proliferation was suspected. However, systemic investigations identified no malignancy. In consideration of the above findings, choroidal inflammation was thought to be the major cause of this condition., Interventions: The patient was administered intensive systemic steroids. Over the next 2 months, the amount of steroid was tapered off., Outcomes: After administration, the bilateral diffuse RPE proliferation settled down. During the 2-year follow-up, there was no recurrence of ocular inflammation and diffuse RPE proliferation, or any other malignancy found., Lessons: This finding demonstrates that bilateral diffuse RPE proliferation can be generated as a secondary phenomenon of choroidal inflammation in patients with a non-malignant status.

Use of biologics has been widely advocated for inflammatory diseases recently. Anti-tumor necrosis factor (TNF)-α antibody therapy is reportedly effective against ocular inflammation. However, side effects of TNF-α inhibition have been reported, particularly in the form of exacerbation of infections such as tuberculosis. Paradoxical reactions such as exacerbated inflammation are also well known. Around 20 million humans are infected with human T-cell leukemia virus type 1 (HTLV-1) globally, and this virus can cause adult T-cell leukemia, HTLV-1-associated myelopathy and HTLV-1 uveitis. As for ophthalmic concerns, it has not been identified whether anti-TNF-α antibody stimulates HTLV-1-infected cells and ocular cells to induce HTLV-1 uveitis in HTLV-1 carriers. Here we investigated the effects of anti-TNF-α antibody on ocular status under HTLV-1 infectious conditions using ocular cells and HTLV-1-infected cells in vitro . We used the ARPE-19 human retinal pigment epithelial cell line as ocular cells considered to play an important role in the blood-ocular barrier, and the MT2 HTLV-1-infected cell line. Jurkat cells were used as controls. Infliximab (IFX) was used as an anti-TNF-α antibody to achieve TNF-α inhibition. We evaluated the production of inflammatory cytokines and intercellular adhesion molecule (ICAM)-1, proliferation of ARPE-19, expression of TNF-α receptor (TNF-R) and HTLV-1 proviral DNA, and the percentage of apoptotic ARPE-19. Inflammatory cytokines such as interleukin (IL)-6, IL-8, TNF, and ICAM-1 were significantly elevated through contact between ARPE-19 and MT2. Treatment with IFX tented to inhibit TNF production, although the level of production was low, but changes in IL-6, IL-8, and ICAM-1 remained unaffected. Expression of TNFR was unaltered by IFX treatment. HTLV-1 proviral DNA was not significantly changed with treatment. No change in cell growth rate or apoptotic rate of ARPE-19 was seen with the addition of IFX. In conclusion, IFX did not exacerbate production of inflammatory cytokines, and did not affect expression of TNFR, proliferation of ARPE-19, HTLV-1 proviral load, or apoptosis of ARPE-19. These results suggest that IFX does not exacerbate HTLV-1-related inflammation in the eye and represents an acceptable treatment option under HTLV-1 infectious conditions., (Copyright © 2019 Uchida, Kamoi, Ando, Wei, Karube and Ohno-Matsui.)

Noninfectious uveitis (NIU), which pathogenesis is often autoimmune nature, occurs as a symptom of systemic syndromes or only in the eye. The standard treatment of NIU is local, topical, and oral administration of corticosteroids (CS) in combination with immunomodulatory therapy (IMT). However, additional therapeutic strategies involving topical and systemic administration of CS or others to treat relapse or exacerbation of ocular inflammation in NIU which present as various ocular manifestations have not been established. The aim of this study was to investigate therapeutic strategies used for various ocular inflammations in relapse or exacerbation of NIU and to evaluate factors associated with the treatment pattern in Japan. The subjects were 198 eyes of 156 NIU patients with relapse or exacerbation of ocular inflammation at 6 university hospitals in Japan. The most frequent disease was sarcoidosis in 23.7% of the cases, followed by Behçet disease (BD) in 21.2%, Vogt-Koyanagi-Harada (VKH) disease in 13.6%, acute anterior uveitis (AAU) in 5.6%, tubulointerstitial nephritis and uveitis syndrome (TINU) in 4.0%, and juvenile idiopathic arthritis (JIA)-associated uveitis in 3.0%. Common ocular findings were worsened anterior inflammation (AI) in 67.2% of the cases, vitreous opacity (VO) in 46.5%, macular edema (ME) in 26.8%, retinal vasculitis (RV) in 23.7%, serous retinal detachment (SRD) in 9.1%, and optic perineuritis (OPN) in 4.0%. Reinforcement of betamethasone eye drop (ED) monotherapy for only AI in both unilateral and bilateral AI, sub-tenon injection of triamcinolone acetonide (STTA) for unilateral posterior inflammation including VO and ME, and systemic therapy using CS and/or IMT for bilateral anterior and posterior inflammation were significantly more frequent. Frequencies of exacerbated individual ocular findings in sarcoidosis and BD were similar, and severe ocular inflammation associated with panuveitis required both topical and systemic therapies. These results demonstrate that reinforcement of betamethasone EDs, topical administration of triamcinolone acetonide, and long-term administration of systemic corticosteroids are the major therapeutic strategies, and reinforcement of betamethasone EDs was used for exacerbated AI independently from its use for posterior inflammation. In addition, STTA was preferentially used for VO and ME associated with posterior inflammation.

We investigated the clinical characteristics of cilioretinal arteries (CAs) and cilioretinal veins (CVs) in eyes with pathologic myopia. Ninety-five eyes with pathologic myopia and CAs were studied. The retrobulbar vessels from which the CAs originated were identified by indocyanine green angiography (ICGA). The results showed that 114 CAs were identified in the 95 eyes. ICGA showed that 60% of the CAs branched directly off the short posterior ciliary arteries (SPCAs) and 40% originated from the Zinn-Haller arterial circle (ZHAC). The SPCA-derived CAs tended to be located superiorly and served a large retinal area whereas the ZHAC-associated CAs tended to be located temporally and served mainly the macular area. In 15% of the 95 eyes, the CVs were observed to run parallel to the CAs. The CVs exited the eye at the same point where the CAs entered the eye. This study showed that CAs in eyes with pathologic myopia can be divided into those that are SPCA-derived and tend to emerge in the superior optic disc sector, and those that are ZHAC-associated and usually emerge temporally. An elongating peripapillary scleral flange in eyes with progressive axial myopia may lead to a change of chorioretinal vascular system.

Adult T-cell leukemia/lymphoma (ATL) is a rare and aggressive T-cell malignancy with a high mortality rate, resulting in a lack of information among ophthalmologists. Here, we investigated the state of ophthalmic medical care for ATL and ATL-related ocular manifestations by conducting the first large-scale nationwide survey in Japan. A total of 115 facilities were surveyed, including all university hospitals in Japan that were members of the Japanese Ophthalmological Society and regional core facilities that were members of the Japanese Ocular Inflammation Society. The collected nationwide data on the state of medical care for ATL-related ocular manifestations and ATL-associated ocular findings were categorized, tallied, and analyzed. Of the 115 facilities, 69 (60%) responded. Overall, 28 facilities (43.0%) had experience in providing ophthalmic care to ATL patients. ATL-related ocular manifestations were most commonly diagnosed "based on blood tests and characteristic ophthalmic findings." By analyzing the 48 reported cases of ATL-related ocular manifestations, common ATL-related ocular lesions were intraocular infiltration (22 cases, 45.8%) and opportunistic infections (19 cases, 39.6%). All cases of opportunistic infection were cytomegalovirus retinitis. Dry eye (3 cases, 6.3%), scleritis (2 cases, 4.2%), uveitis (1 case, 2.1%), and anemic retinopathy (1 case, 2.1%) were also seen. In conclusion, intraocular infiltration and cytomegalovirus retinitis are common among ATL patients, and ophthalmologists should keep these findings in mind in their practice.

Rationale: Dengue fever is a notable emerging infectious disease that is now seen worldwide, with an estimated incidence of approximately 390 million cases per year. Although ocular complications are uncommon among dengue fever-infected patients, caution is needed to prevent vision loss. Here we report a potentially serious sight-threatening complication of dengue fever, dengue fever-associated necrotizing scleritis., Patient Concerns and Diagnosis: After being bitten by mosquitoes, a 60-year-old Japanese female exhibited positive serologic tests of immunoglobulin M and G enzyme immunoassays for dengue viral infection along with a decrease of leukocytes and platelets. These findings led to a dengue fever diagnosis. Slit lamp examination of her left eye revealed a conjunctival and scleral injection, elevation of the entire circumference of the sclera, and bulging of the sclera on the nasal upper side with a patch of avascular episcleral tissue. Since additional systemic examinations identified no autoimmune diseases such as rheumatism, we diagnosed the patient as dengue fever-associated scleritis., Interventions: Intensive systemic and topical steroids were administrated during the initial acute phase. Over the next 15 months, the amount of steroid was tapered off., Outcome: Initial findings for the scleritis gradually declined in response to steroid treatment. Although there was no recurrence of active scleritis, gradual thinning of the sclera continued to occur during the 18-year follow-up., Lessons: To the best of our knowledge, this is the first reported case of dengue fever-associated necrotizing scleritis with long-term follow-up. This case suggests the existence of a long-term immune-mediated mechanism during the development of the dengue fever-associated necrotizing scleritis. Dengue fever virus patients found to have red eyes need to be carefully followed and treated, as these eyes might develop thinning of the sclera that could lead to rupture of the globe, thereby resulting in blindness.

Background: Graves' disease is an autoimmune thyroid disorder characterized by hyperthyroidism, and patients exhibit thyroid-stimulating hormone receptor antibody. The major methods of measuring circulating thyroid-stimulating hormone receptor antibody include the thyroid-stimulating hormone-binding inhibitory immunoglobulin assays. Although the diagnostic accuracy of these assays has been improved, a minority of patients with Graves' disease test negative even on second-generation and third-generation thyroid-stimulating hormone-binding inhibitory immunoglobulins. We report a rare case of a thyroid-stimulating hormone-binding inhibitory immunoglobulin-positive patient with Graves' disease who showed rapid lowering of thyroid-stimulating hormone-binding inhibitory immunoglobulin levels following administration of the anti-thyroid drug thiamazole, but still experienced Graves' hyperthyroidism., Case Presentation: A 45-year-old Japanese man presented with severe hyperthyroidism (serum free triiodothyronine >25.0 pg/mL; reference range 1.7 to 3.7 pg/mL) and tested weakly positive for thyroid-stimulating hormone-binding inhibitory immunoglobulins on second-generation tests (2.1 IU/L; reference range <1.0 IU/L). Within 9 months of treatment with oral thiamazole (30 mg/day), his thyroid-stimulating hormone-binding inhibitory immunoglobulin titers had normalized, but he experienced sustained hyperthyroidism for more than 8 years, requiring 15 mg/day of thiamazole to correct. During that period, he tested negative on all first-generation, second-generation, and third-generation thyroid-stimulating hormone-binding inhibitory immunoglobulin assays, but thyroid scintigraphy revealed diffuse and increased uptake, and thyroid ultrasound and color flow Doppler imaging showed typical findings of Graves' hyperthyroidism., Conclusions: The possible explanations for serial changes in the thyroid-stimulating hormone-binding inhibitory immunoglobulin results in our patient include the presence of thyroid-stimulating hormone receptor antibody, which is bioactive but less reactive on thyroid-stimulating hormone-binding inhibitory immunoglobulin assays, or the effect of reduced levels of circulating thyroid-stimulating hormone receptor antibody upon improvement of thyroid autoimmunity with thiamazole treatment. Physicians should keep in mind that patients with Graves' disease may show thyroid-stimulating hormone-binding inhibitory immunoglobulin assay results that do not reflect the severity of Graves' disease or indicate the outcome of the disease, and that active Graves' disease may persist even after negative results on thyroid-stimulating hormone-binding inhibitory immunoglobulin assays. Timely performance of thyroid function tests in combination with sensitive imaging tests, including thyroid ultrasound and scintigraphy, are necessary to evaluate the severity of Graves' disease and treatment efficacy.